A fresh look at mental illness: Researcher points toward a new way to classify disorders

Peter Reuell, Jul 31, Harvard Gazette

clipped article:

Ask Assistant Professor of Psychology Joshua Buckholtz to explain his research into mental disorders, and he’ll likely start with a question that’s got more to do with basic medicine: When is the flu appendicitis?

The answer, of course, is never. Each is associated with a very specific — and nonoverlapping — set of biological causes and effects. Understanding what these are, Buckholtz explained, allows doctors to discriminate between the two with near-perfect accuracy.

Unfortunately, Buckholtz said, the same cannot be said for mental disorders.

According to Buckholtz, meeting the diagnostic criteria for multiple psychiatric disorders is the rule, rather the exception.

“This tells us that there are either a lot of people who are unlucky enough to be afflicted with multiple distinct, unique disorders at the same time, or that something is very wrong with our method for classifying psychological disorders.”

In a June 21 paper published in Neuron, Buckholtz and co-author Andreas Meyer-Lindenberg, a researcher from the Central Institute of Mental Health and the University of Heidelberg in Germany, identify a biological reason for that disconnect. Extrapolating from what we know about the genetic causes of mental illness and their effects on the brain, they propose that many mental disorders appear to share symptoms because genes for mental illness cause changes in key brain circuits that affect a wide range of cognitive processes.

“Individual genetic differences cause variability in the way that brain circuits function,” he continued. “These differences in brain circuit function lead to the wide range of variation in cognitive, emotional, motivation, and social function that we see in people all around us. The specific genes that are involved, and the way that these genes interact with the environments to which we are exposed, determine how specific brain circuits behave. When those circuits don’t function well, this is expressed as a deficit in whatever domain of cognition is supported by the ‘sick’ circuit. When these deficits cause dysfunction in everyday life, we call it a symptom. When those symptoms become impairing enough, someone comes to the clinic and receives a diagnosis.”

“What we can say is that genetic and environmental risk factors for mental illness produce graded changes in the function of one or more brain circuits, producing graded changes in cognitive processes supported by those circuits,” Buckholtz said. “The changes in those cognitive processes will produce varying expression of symptoms that are shared across multiple disorders.”

One possible impact of the paper’s findings, Buckholtz said, could come as researchers work to design a new way to classify mental disorders.

The Journal of Child Psychology and Psychiatry study of 40 girls revealed brains of teenage girls with behavioural disorders are different to those of their peers.

The team found part of the brain called the amygdala was smaller in the brains of male and female teenagers with conduct disorder than in their peers.

Girls with conduct disorder also had less grey matter in an area of the brain called the insula - linked to emotion and understanding your own emotions.

"In the US, people are already using brain scans to argue diminished responsibility. I think we're too early in our understanding to really do that, but it is happening.-Dr Graeme Fairchild, of the University of Cambridge

"It suggests that at least a component of this has a biological basis - and there are people who don't believe there is one."-Dr Michael Craig of King's College London's Institute of Psychiatryhttp://www.bbc.co.uk/news/health-20002093

Uncovering secrets of
how intellect and behavior emerge during childhood

November 8, 2012 in Medical Xpress, Genetics

Scientists from the Florida
campus of The Scripps Research Institute (TSRI) have shown that a single
protein plays an oversized role in
intellectual and behavioral development. The scientists found that
mutations in a single gene, which is known to cause intellectual disability and
increase the risk of developing autism spectrum disorder, severely disrupts the
organization of developing brain circuits during early childhood. This study
helps explain how genetic mutations can
cause profound cognitive and behavioral problems.

The study focused on a critical synaptic protein known as
SynGAP1.

"There are a few genes that can't be altered without
affecting normal cognitive abilities," Rumbaugh said. "SynGAP1 is one
of the most important genes in cognition—so far, every time a mutation that
disrupts the function of SynGAP1 has been found, that individual's brain simply
could not develop correctly. It regulates
the development of synaptic function like no other gene I've seen."

Interestingly, inducing these mutations after the critical
development period was complete had virtually no impact on normal synapse
function and repairing these pathogenic mutations in adulthood did not improve
behavior or cognition.

"A key finding is we were able to remove the mutation
and restore SynGAP protein levels in adult mice with obvious cognitive and
behavioral problems, but this intervention did not benefit the animals,"
Rumbaugh said. These results imply that very early intervention is essential in
neurodevelopmental disorders, particularly for cognitive problems. The team is
now aggressively searching for the optimal period during development in which
repairing these mutations is most beneficial.

Novel studies of gene
regulation in brain development may mean new treatment of mental disorders

December 2, 2012 in
Medical Xpress, Genetics

modified

Researchers at the University of California, San Diego and
the Institut Pasteur, Paris identified the hierarchical tree of CGG–TF networks
that determine the patterns of genes expressed during brain development and
found that some "master
transcription factors" at the top level of the hierarchy regulated the
expression of a significant number of gene groups.

Instead of a taking
the approach that a single gene creates a single response, researchers used
contemporary methods of data analysis, along with the Gordon supercomputer at
the university's San Diego Supercomputer Center (SDSC), to identify CGGs
responsible for brain development which can be affected for treatment of mental
disorders. The team found that these groups of genes act in concert to send
signals at various levels of the hierarchy to other groups of genes, which
control the general and more specific (depending of the level) events in brain
structure development.

"We have proposed a novel, though still hypothetical,
strategy of drug design based on this hierarchical network of TFs that could
pave the way for a new category of pharmacological
agents that could be used to block a pathway at a critical time during brain
development as an effective way to treat and even prevent mental disorders
such as ASD and schizophrenia," said lead author Igor Tsigelny, a research
scientist with SDSC, as well as the university's Moores Cancer Center and
Department of Neurosciences. "On a broader scale, these findings have the
potential to change the paradigm of drug design."

About Me

First things first, that's not a picture of me, although it could be any one of us. It's a painting by Alex Grey.
Next, the blog Limbic Signal is an extension of my book Hidden Scents, and the blog Network Address is a personal archive that I like to keep online for easy access.
Last, I'm a thirty-something male from Suburbia, New Jersey, a high school visual arts instructor, independent researcher, and writer.
Hidden Scents The Language of Smell in the Age of Approximation is my first attempt at authoring a work of non-fiction, and serves as a response to the dearth of information on the topic of Smell.